大鼠脊髓5－羟色胺1A受体和1C／2受体亚型参与高频电针镇痛

通过脊髓蛛网膜下腔慢性埋植导管分别注射５－ＨＴ受体的多种拮抗剂，分析了大鼠脊髓５－ＨＴ受体的三个主要类型５－ＨＴ１、５－ＨＴ２和５－ＨＴ３受体在高频电针镇痛中的作用。实验结果表明：ｉ．ｔ．注射５－ＨＴ１Ａ受体拮抗剂ｓｐｉｐｅｒｏｎｅ２５μｇ不影响１００Ｈｚ电针的平均针效（Ｐ＞０．０５），但可阻断电针后效应（Ｐ＜０．０１）；ｉ．ｔ．注射５－ＨＴ１ｃ／２受体拮抗剂ｍｉａｎｓｅｒｉｎ５０μｇ可阻断１００Ｈｚ电针的平均针效，也可阻断电针后效应（Ｐ＜０．０１）；ｉ．ｔ．注射５－ＨＴ２受体拮抗剂１－ＮＰ２０μｇ和５－ＨＴ３受体拮抗剂ＩＣＳ２０５－９３０１００μｇ对１００Ｈｚ电针镇痛没有显著影响（Ｐ＞０．０５）。提示大鼠脊髓５－ＨＴ１Ａ受体和５－ＨＴ１ｃ／２受体参与介导１００Ｈｚ电针镇痛，而５－ＨＴ３受体可能不起主要作用。     

Upregulation of P2X3 receptors by neuronal calcium sensor protein VILIP-1 in dorsal root ganglions contributes to the bone cancer pain in rats

Primary and metastatic cancers that affect bone are frequently associated with severe and intractable pain. The mechanisms underlying the development of bone cancer pain are largely unknown. In this study, we first demonstrated that a functional upregulation of P2X3 receptors in dorsal root ganglion (DRG) neurons is closely associated with the neuronal hyperexcitability and the cancer-induced bone pain in MRMT-1 tumor cell–inoculated rats. Second, we revealed that visinin-like protein 1 (VILIP-1), a member of visinin-like proteins that belong to the family of neuronal calcium sensor proteins is responsible for the observed upregulation of P2X3 receptors in DRG neurons. The interaction between the amino terminus of VLIP-1 and the carboxyl terminus of the P2X3 receptor is critical for the surface expression and functional enhancement of the receptor. Finally, overexpression of VILIP-1 increases the expression of functional P2X3 receptors and enhances the neuronal excitability in naive rat DRG neurons. In contrast, knockdown of VILIP-1 inhibits the development of bone cancer pain via downregulation of P2X3 receptors and repression of DRG excitability in MRMT-1 rats. Taken together, these results suggest that functional upregulation of P2X3 receptors by VILIP-1 in DRG neurons contributes to the development of cancer-induced bone pain in MRMT-1 rats. Hence, P2X3 receptors and VILIP-1 could serve as potential targets for therapeutic interventions in cancer patients for pain management. Pharmacological blockade of P2X3 receptors or knockdown of VILIP-1 in DRGs would be used as innovative strategies for the treatment of bone cancer pain.     

手针、电针及经皮穴位电刺激调节人脑功能的功能性磁共振观察

目的:比较不同的针刺方法对人脑功能的调节作用。方法:16名健康成年被试(男8例),每名被试均参加4次实验,分别接受手针、电针、经皮穴位电刺激及触觉对照刺激,在刺激过程中同时进行功能性磁共振(血氧依赖水平,blood oxygen level dependent,BOLD)数据采集。结果:4种刺激均表现为对躯体运动感觉系统、岛叶和小脑的BOLD信号激活。此外,电针还表现为对边缘系统的BOLD信号的抑制,而经皮穴位电刺激则特异性地激活了基底核(P<0.001,uncorrected,k>22)。结论:电针和经皮穴位电刺激可模拟手针对脑BOLD信号的调节作用,表明3者有其共性,又各具特色。其生理意义有待进一步阐明。     

催产素在孤独症患者社交障碍中的作用及治疗潜能(综述)

孤独症是一种原因不明的广泛性神经发育障碍性疾病,至今尚无有效的治疗方法。作为孤独症的特征性症状之一,社交障碍严重影响患者的身心健康与生活质量。研究显示,催产素在社会交往中发挥重要作用,而催产素缺乏或利用不足可能与孤独症患者的社交障碍有关。本文总结了近年来关于催产素与孤独症社交障碍的研究进展,并提出催产素用于孤独症临床治疗的可能性,希望能够对孤独症的研究和治疗提供帮助。     

韩氏穴位神经刺激仪对妇科腹腔镜术后疼痛与恶心呕吐的影响

目的:观察在妇科腹腔镜术前、后使用韩氏穴位神经刺激仪(Han’s Acupoint Nerve Stimulator,HANS),对术后疼痛与恶心呕吐症状的影响。方法:接受妇科腹腔镜手术患者91例,随机分配到3组:A组为术前30分钟使用安慰剂HANS,B组为术前30分钟使用HANS,C组为手术前与术后30分钟各使用HANS 30分钟。频率:2/100 Hz,取穴:一侧合谷-劳宫,对侧内关-外关。采用视觉模拟尺(visual analogue scale,VAS)在术后0.5、6、24小时分别评估患者疼痛与恶心呕吐的程度。结果:与A组比较,B组与C组在术后0.5、6、24小时的疼痛症状均有显著改善;也能显著改善术后30分钟时恶心呕吐症状。C组的治疗作用似优于B组,但差异未达显著水平。结论:术前使用,或者术前加术后使用HANS,能有效降低妇科腹腔镜术后疼痛与恶心呕吐症状。     

组蛋白去乙酰化酶2基因在苯并（a）芘致神经细胞凋亡中的量效和时效表达

[目的]通过体外培养细胞途径研究组蛋白去乙酰化酶2（HDAC2）基因在苯并（a）芘[B（a）P]所致神经细胞凋亡中的量效和时效表达。[方法]大鼠原代培养的神经元细胞分为两批：第一批分4个组,以B（a）P同时加入s9对细胞染毒,分别为二甲基亚砜（DMSO）组、低剂量组、中剂量组、高剂量组,使其终浓度为0、10、20、40gmol／L,继续培养48h;第二批分5个组,以20gmol／LB（a）P染毒,分别于染毒0、6、12、24、48h处理细胞。用流式细胞术检测神经细胞的凋亡率,实时荧光定量PCR法检测caspase-3,HDAC2基因的量效和时效表达情况。[结果]①流式细胞术结果显示,与DMSO组相比,中、高剂量组神经细胞的凋亡率明显增加（P〈O．05）;与低剂量组相比,高剂量组凋亡率增加（P〈0．05）。与0h组相比,染毒24、48h组神经细胞的凋亡率明显增加（P〈0．05）。②与DMSO组相比,高剂量组caspase-3、HDAC2mRNA的表达量明显增加（P〈0．01）;与低剂量组相比,高剂量组caspase-3mRNA表达量明显增加（P〈0．05）。与0h组相比,染毒48h组caspase-3、HDAC2mRNA表达量明显升高（P〈0．01,P〈0．05）。[结论]B（a）P可引起神经细胞凋亡,HDAC2基因表达上升,该基因可能在B（a）P所导致的神经细胞凋亡中起重要作用。     

Genetic diagnosis strategy of hereditary non-polyposis colorectal cancer

AIM： To study the characteristics of mismatch repair gene mutation of Chinese hereditary non-polyposis colorectal cancer （HNPCC） and hMLH1 gene promoter methylation, and to improve the screening strategy and explore the pertinent test methods. METHODS： A systematic analysis of 30 probands from HNPCC families in the north of China was performed by immunohistochemistry, microsatellite instability （MSI）, gene mutation and methylation detection. RESULTS： High frequency microsatellite instability occurred in 25 probands （83.3%） of HNPCC family. Loss of hMLH1 and hMSH2 protein expression accounted for 88% of all microsatellite instability. Pathogenic mutation occurred in 14 samples and 3 novel mutational sites were discovered. Deletion of exons 1-6, 1-7 and 8 of hMSH2 was detected in 3 samples and no large fragment deletion was found in hMLH1. Of the 30 probands, hMLH1 gene promoter methylation occurred in 3 probands. The rate of gene micromutation detection combined with large fragment deletion detection was 46.7%-56.7%. The rate of the two methods in combination with methylation detection was 63.3%. CONCLUSION： Scientific and rational detection strategy can improve the detection rate of HNPCC. Based on traditional molecular genetics and combined with epigenetics, multiple detection methods can accurately diagnose HNPCC.     

Genes Related to Oxytocin and Arginine-Vasopressin Pathways: Associations with Autism Spectrum Disorders

Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorders characterized by impaired social interactions, communication deficits, and repetitive behavior. Although the mechanisms underlying its etiology and manifestations are poorly understood, several lines of evidence from rodent and human studies suggest involvement of the evolutionarily highly-conserved oxytocin (OXT) and arginine-vasopressin (AVP), as these neuropeptides modulate various aspects of mammalian social behavior. As far as we know, there is no comprehensive review of the roles of the OXT and AVP systems in the development of ASD from the genetic aspect. In this review, we summarize the current knowledge regarding associations between ASD and single-nucleotide variants of the human OXT-AVP pathway genes OXT, AVP, AVP receptor 1a (AVPR1a), OXT receptor (OXTR), the oxytocinase/vasopressinase (LNPEP), and ADP-ribosyl cyclase (CD38).     

丙型肝炎病毒核心蛋白诱导人胆管上皮细胞转化及成瘤实验

目的　探讨丙型肝炎病毒核心蛋白 (HCV -C)对人胆管上皮细胞 (BEC)的转化及致癌作用。方法　通过脂质体介导将含有HCV- C基因重组真核表达载体pcDNAHCV- C导入BEC细胞,G418筛选表达目的基因的细胞;聚合酶链反应 (PCR)及免疫组织化学SABC法检测细胞中HCV -C基因及蛋白的表达;细胞计数、锚着非依赖性生长实验、成瘤性检测等鉴定其生物学行为变化,免疫组织化学SABC法检测所致肿瘤组织中HCV- C蛋白表达。结果　HCV -C转染的BEC细胞中HCV- C蛋白表达于胞质,质粒pcDNAHCV C转染细胞的倍增时间较pcDNA3转染细胞和未转染BEC细胞明显缩短(分别为 14h, 28h, 30h)。pcDNAHCV C和pcDNA3转染细胞及未转染BEC在软琼脂中的克隆形成率分别为 36. 0%、2 .5%和 1 5% (P<0. 01)。3种细胞接种裸鼠后,pcDNAHCV C转染细胞注射组出现肿瘤,病理学检查证实为胆管细胞癌,肿瘤组织有HCV- C蛋白的表达。而pcDNA3转染细胞及未转染BEC细胞注射组在注射 36d后仍未见肿瘤发生。结论　HCV- C蛋白具有促胆管细胞转化和促进肿瘤发生的作用。